The long term goal of this project is to determine the mechanism by which nerve dysfunction results in chronic neuropathic pain. The objective of this proposal is: (1) to understand the modulatory actions of opioids on excitatory amino acid-evoked (EAA) responses in trigeminal neurons; and (2) to define the role of opioids in generating and maintaining the sustained responses to EAA. We hypothesize that binding of an opioid activates G proteins which in turn raise the level of second messengers inside the cell and result in a change in the EAA-evoked responses. The experiments are designed to test this hypothesis. The EAA-activated currents will be measured using the patch clamp technique. Experiments will be performed on trigeminal neurons, labeled trigeminothalamic cells isolated from the spinal trigeminal subnucleus caudalis and the same type of neurons in thin medullary slices. The information obtained from this project will advance our understanding of the pain mechanism and help us design a better therapy for treatment of neuropathic pain.